Research ArticleMICROBIOME

Cell surface polysaccharides of Bifidobacterium bifidum induce the generation of Foxp3+ regulatory T cells

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Science Immunology  19 Oct 2018:
Vol. 3, Issue 28, eaat6975
DOI: 10.1126/sciimmunol.aat6975

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Deconstructing probiotics

Besides supporting host metabolism, our intestinal microbiota also play a vital role in modulating functions of immune cells in the gut. Here, Verma et al. have examined how a particular probiotic strain, Bifidobacterium bifidum, promotes the generation of T regulatory (Treg) cells in the intestine. They have identified β-glucan/galactan polysaccharides derived from the cell wall of B. bifidum to be responsible for promoting Treg cell induction in the intestine. Further, they report this process to be dependent on intestinal dendritic cells that express Toll-like receptor 2. Studies such as this open up the possibility of using microbial components rather than live microbes to treat microbial dysbiosis associated with gastrointestinal disorders including colitis and Crohn’s disease.

Abstract

Dysregulation of intestinal microflora is linked to inflammatory disorders associated with compromised immunosuppressive functions of Foxp3+ T regulatory (Treg) cells. Although mucosa-associated commensal microbiota has been implicated in Treg generation, molecular identities of the “effector” components controlling this process remain largely unknown. Here, we have defined Bifidobacterium bifidum as a potent inducer of Foxp3+ Treg cells with diverse T cell receptor specificity to dietary antigens, commensal bacteria, and B. bifidum itself. Cell surface β-glucan/galactan (CSGG) polysaccharides of B. bifidum were identified as key components responsible for Treg induction. CSGG efficiently recapitulated the activity of whole bacteria and acted via regulatory dendritic cells through a partially Toll-like receptor 2–mediated mechanism. Treg cells induced by B. bifidum or purified CSGG display stable and robust suppressive capacity toward experimental colitis. By identifying CSGG as a functional component of Treg-inducing bacteria, our studies highlight the immunomodulatory potential of CSGG and CSGG-producing microbes.

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